Summary of Work: This project is intended to increase our understanding of the use and application of mathematical and statistical models in toxicology and biochemistry and to implement these mathematical models to aid in explaining current research findings. The research effort explores a diverse range of biological areas, including carcinogenesis, pharmacology, developmental biology, neurology, immunology and endocrinology. Major accomplishments include (1) A comprehensive, biologically based mathematical model was developed for the rat estrus cycle (2) A model was developed which describes the important factors for priming hepatocytes to enter the G1 phase of the cell cycle (3) Methods were developed for the backcalculation of exposures in an occupational cohort (4) An NTP study, designed around a PBPK model, of transgenic animals exposed to 2,3,7,8-TCDD was analyzed using a two-stage and a three-stage model (5) A biologically-based model was developed for developmental toxicity (6) Data on morbidity for the city of Tokyo from 1980 to 1994 were analyzed to determine the effects of daily temperatures and air pollutant concentrations (NO2, O3 and PM10) on heat stress and related diseases (7) The impact of polymorphisms on the estimation of risks in a general population were explored (8) developed methods for evaluating the adequacy of benchmark doses, (9) continued to aid in the scientific improvement of risk assessment methods through the application of sound science to key environmental issues such as exposure to TCDD, aflatoxins and endocrine disruptors.